PROMOTION-LIKE ENHANCEMENT OF TRACHEAL CARCINOGENESIS IN RATS BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (12) , 4352-4355
Abstract
Experiments were conducted to determine whether 2-stage carcinogenesis could be observed in rat tracheal epithelium using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. Heterotopic tracheal transplants in Fischer 344 rats were first exposed to 188 .mu.g of DMBA delivered over 4 wk and subsequently to 100 .mu.g of TPA. The TPA was released from beeswax pellets at a rate of 1.1 .mu.g/day during the first 2 mo. and at a rate of 0.3 .mu.g/day for the subsequent 2 mo. TPA alone caused marked inflammation and epithelial hyperplasia in tracheal grafts but no metaplastic or dysplastic changes. The tumor incidence in tracheas exposed to DMBA only was 20%; that in tracheas exposed to DMBA followed by TPA was 72%. TPA also accelerated the appearance of tumors. The mean tumor induction time in the group exposed to DMBA only was 91 wk as compared to 75 wk in the group exposed to DMBA and TPA. TPA enhances the tracheal tumor response in a manner similar to that of tumor promotion in mouse skin.